Arthritis will be induced in mice by intradermal injection of Chick, Bovine, Rat, or Mouse Type II collagen. Assessment of arthritis in the mouse will be accomplished by clinical inspection of the animals, measurement of joint swelling, X-ray and histological analysis of the joints. The genetics of CIA will be studied using inbred mice with varying background genes, independent haplotype mice congenic to the C57BL/10, C57GL/6, and C3H background, recombinant strains, and mutants. The inheritance of the disease will be studied by F1, F2 and backcross combinations. The humoral response to Type II collagen will be assessed in relation to CIA. The level of IgG and IgM antibodies will be measured by radio-immunoassay. Antisera will be investigated for cross-reactivity and auto-reactivity against the four species of Type II collagen. The cellular response to Type II collagen will be assessed in relation to CIA, with both the in vitro (T-cell proliferation) and the in vivo (radiometric ear assay) responses being monitored. The various subpopulations of cells involved in the response will be identified. Passive transfer of CIA will be investigated using cell and immunoglobulin transfer. This may elucidate the contribution of various cell and antibody responses to collagen relevant in the disease. Precise epitope specificity for different collagen antigens will be studied by the production of monoclonal anti-collagen antibodies, and collagen-reactive T-cell clones from CIA susceptible and resistant mice. The relationship of genetic markers of mouse CIA and human rheumatoid arthritis (RA) will be investigated by cross-reactivity studies utilizing specific sera and cloned T-cells. Drug studies using the CIA mouse model will investigate the genetic control of drug responsiveness and toxic reactions during treatment of inflammatory disease.